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Displays are basic building blocks of modern electronics1,2. Integrating displays into textiles offers exciting opportunities for smart electronic textiles-the ultimate goal of wearable technology, poised to change the way in which we interact with electronic devices3-6. Display textiles serve to bridge human-machine interactions7-9, offering, for instance, a real-time communication tool for individuals with voice or speech difficulties. Electronic textiles capable of communicating10, sensing11,12 and supplying electricity13,14 have been reported previously. However, textiles with functional, large-area displays have not yet been achieved, because it is challenging to obtain small illuminating units that are both durable and easy to assemble over a wide area. Here we report a 6-metre-long, 25-centimetre-wide display textile containing 5 × 105 electroluminescent units spaced approximately 800 micrometres apart. Weaving conductive weft and luminescent warp fibres forms micrometre-scale electroluminescent units at the weft-warp contact points. The brightness between electroluminescent units deviates by less than 8 per cent and remains stable even when the textile is bent, stretched or pressed. Our display textile is flexible and breathable and withstands repeated machine-washing, making it suitable for practical applications. We show that an integrated textile system consisting of display, keyboard and power supply can serve as a communication tool, demonstrating the system's potential within the 'internet of things' in various areas, including healthcare. Our approach unifies the fabrication and function of electronic devices with textiles, and we expect that woven-fibre materials will shape the next generation of electronics.
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Terminais de Computador , Eletrônica/instrumentação , Têxteis , Humanos , Maleabilidade , Dispositivos Eletrônicos VestíveisRESUMO
Cross-linkers play a critical role in capturing protein dynamics in chemical cross-linking mass spectrometry techniques. Various types of cross-linkers with different backbone features are widely used in the study of proteins. However, it is still not clear how the cross-linkers' backbone affect their own structure and their interactions with proteins. In this study, we systematically characterized and compared methylene backbone and polyethylene glycol (PEG) backbone cross-linkers in terms of capturing protein structure and dynamics. The results indicate the cross-linker with PEG backbone have a better ability to capture the inter-domain dynamics of calmodulin, adenylate kinase, maltodextrin binding protein and dual-specificity protein phosphatase. We further conducted quantum chemical calculations and all-atom molecular dynamics simulations to analyze thermodynamic and kinetic properties of PEG backbone and methylene backbone cross-linkers. Solution nuclear magnetic resonance was employed to validate the interaction interface between proteins and cross-linkers. Our findings suggest that the polarity distribution of PEG backbone enhances the accessibility of the cross-linker to the protein surface, facilitating the capture of sites located in dynamic regions. By comprehensively benchmarking with disuccinimidyl suberate (DSS)/bis-sulfosuccinimidyl-suberate(BS3), bis-succinimidyl-(PEG)2 revealed superior advantages in protein dynamic conformation analysis in vitro and in vivo, enabling the capture of a greater number of cross-linking sites and better modeling of protein dynamics. Furthermore, our study provides valuable guidance for the development and application of PEG backbone cross-linkers.
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Polietilenoglicóis , Proteínas , Polietilenoglicóis/química , Proteínas/química , Espectrometria de Massas , Conformação Proteica , Simulação de Dinâmica MolecularRESUMO
This study outlines the preparation and characterization of a unique superlattice composed of indium oxide (In2O3) vertex-truncated nano-octahedra, along with an exploration of its response to high-pressure conditions. Transmission electron microscopy and scanning transmission electron microscopy were employed to determine the average circumradius (15.2 nm) of these vertex-truncated building blocks and their planar superstructure. The resilience and response of the superlattice to pressure variations, peaking at 18.01 GPa, were examined using synchrotron-based wide-angle X-ray scattering (WAXS) and small-angle X-ray scattering (SAXS) techniques. The WAXS data revealed no phase transitions, reinforcing the stability of the 2D superlattice composed of random layers in alignment with a p31m planar symmetry as discerned by SAXS. Notably, the SAXS data also unveiled a pressure-induced, irreversible translation of octahedra and ligand interaction occurring within the random layer. Through our examination of these pressure-sensitive behaviors, we identified a distinctive translation model inherent to octahedra and observed modulation of the superlattice cell parameter induced by pressure. This research signifies a noteworthy advancement in deciphering the intricate behaviors of 2D superlattices under a high pressure.
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Membrane channel proteins (MCPs) play key roles in matter transport through cell membranes and act as major targets for vaccines and drugs. For emerging ionic liquid (IL) drugs, a rational understanding of how ILs affect the structure and transport function of MCP is crucial to their design. In this work, GPU-accelerated microsecond-long molecular dynamics simulations were employed to investigate the modulating mechanism of ILs on MCP. Interestingly, ILs prefer to insert into the lipid bilayer and channel of aquaporin-2 (AQP2) but adsorb on the entrance of voltage-gated sodium channels (Nav). Molecular trajectory and free energy analysis reflect that ILs have a minimal impact on the structure of MCPs but significantly influence MCP functions. It demonstrates that ILs can decrease the overall energy barrier for water through AQP2 by 1.88 kcal/mol, whereas that for Na+ through Nav is increased by 1.70 kcal/mol. Consequently, the permeation rates of water and Na+ can be enhanced and reduced by at least 1 order of magnitude, respectively. Furthermore, an abnormal IL gating mechanism was proposed by combining the hydrophobic nature of MCP and confined water/ion coordination effects. More importantly, we performed experiments to confirm the influence of ILs on AQP2 in human cells and found that treatment with ILs significantly accelerated the changes in cell volume in response to altered external osmotic pressure. Overall, these quantitative results will not only deepen the understanding of IL-cell interactions but may also shed light on the rational design of drugs and disease diagnosis.
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Permeabilidade da Membrana Celular , Ativação do Canal Iônico , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Líquidos Iônicos/química , Líquidos Iônicos/metabolismo , Modelos Moleculares , Estrutura Terciária de Proteína , Água/química , Linhagem CelularRESUMO
Chronic psoriasis is a kind of immune-mediated skin illness and the underlying molecular mechanisms of pathogenesis remain incompletely understood. Here, we used small RNA microarray assays to scan the differential expressed RNAs in psoriasis patient samples. The downstream miRNAs and its targets were predicted using bioinformatics analysis from online bases and confirmed using fluorescence in situ hybridization and dualluciferase report gene assay. Cell ability of proliferation and migration were detected using CCK-8 and transwell assays. The results showed that a new snoRNA Snora73 was upregulated in psoriasis patient samples. Overexpression of Snora73 significantly increased psoriasis cells viability and migration, while knockdown of Snora73 got the opposite results. Mechanistically, our results showed that Snora73 acted as a sponge for miR-3074-5p and PBX1 is a direct target of miR-3074-5p in psoriasis cells. Furthermore, miR-3074-5p suppressed psoriasis cell proliferation and migration, while PBX1 promoted cell proliferation and migration in psoriasis. Collectively, these findings reveal a crucial role of Snora73 in progression of psoriasis through miR-3074-5p/PBX1 signaling pathway and suggest a potential therapeutic strategy.
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MicroRNAs , Fator de Transcrição 1 de Leucemia de Células Pré-B , Psoríase , RNA Longo não Codificante , RNA Nucleolar Pequeno , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Hibridização in Situ Fluorescente , MicroRNAs/genética , Psoríase/genética , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno/genética , Fator de Transcrição 1 de Leucemia de Células Pré-B/genéticaRESUMO
Cross-linking mass spectrometry (XL-MS) is a powerful tool for elucidating protein structures and protein-protein interactions (PPIs) at the global scale. However, sensitive XL-MS analysis of mass-limited samples remains challenging, due to serious sample loss during sample preparation of the low-abundance cross-linked peptides. Herein, an optimized miniaturized filter-aided sample preparation (O-MICROFASP) method was presented for sensitive XL-MS analysis of microscale samples. By systematically investigating and optimizing crucial experimental factors, this approach dramatically improves the XL identification of low and submicrogram samples. Compared with the conventional FASP method, more than 7.4 times cross-linked peptides were identified from single-shot analysis of 1 µg DSS cross-linked HeLa cell lysates (440 vs 59). The number of cross-linked peptides identified from 0.5 µg HeLa cell lysates was increased by 58% when further reducing the surface area of the filter to 0.058 mm2 in the microreactor. To deepen the identification coverage of XL-proteome, five different types of cross-linkers were used and each µg of cross-linked HeLa cell lysates was processed by O-MICROFASP integrated with tip-based strong cation exchange (SCX) fractionation. Up to 2741 unique cross-linked peptides were identified from the 5 µg HeLa cell lysates, representing 2579 unique K-K linkages on 1092 proteins. About 96% of intraprotein cross-links were within the maximal distance restraints of 26 Å, and 75% of the identified PPIs reported by the STRING database were with high confidence (scores ≥0.9), confirming the high validity of the identified cross-links for protein structural mapping and PPI analysis. This study demonstrates that O-MICROFASP is a universal and efficient method for proteome-wide XL-MS analysis of microscale samples with high sensitivity and reliability.
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Small extracellular vesicles (sEVs) are proven to hold great promise for diverse therapeutic and diagnostic applications. However, batch preparation of sEVs with high purity and bioactivity is a prerequisite for their clinical translations. Herein, we present an electric field assisted tangential flow filtration system (E-TFF), which integrates size-based filtration with electrophoretic migration-based separation to synergistically achieve the isolation of high-quality sEVs from cell culture medium. Compared with the gold-standard ultracentrifugation (UC) method, E-TFF not only improved the purity of sEVs by 1.4 times but also increased the yield of sEVs by 15.8 times. Additionally, the entire isolation process of E-TFF was completed within 1 h, about one-fourth of the time taken by UC. Furthermore, the biological activity of sEVs isolated by E-TFF was verified by co-incubation of sEVs derived from human umbilical cord mesenchymal stem cells (hUCMSCs) with HT22 mouse hippocampal neuronal cells exposed to amyloid-ß (Aß). The results demonstrated that the sEVs isolated by E-TFF exhibited a significant neuroprotective effect. Overall, the E-TFF platform provides a promising and robust strategy for batch preparation of high-quality sEVs, opening up a broad range of opportunities for cell-free therapy and precision medicine.
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Marine microbes drive pivotal transformations in planetary-scale elemental cycles and have crucial impacts on global biogeochemical processes. Metaproteomics is a powerful tool for assessing the metabolic diversity and function of marine microbes. However, hundreds of liters of seawater are required for normal metaproteomic analysis due to the sparsity of microbial populations in seawater, which poses a substantial challenge to the widespread application of marine metaproteomics, particularly for deep seawater. Herein, a sensitive marine metaproteomics workflow, named sensitive marine metaproteome analysis (SMMP), was developed by integrating polycarbonate filter-assisted microbial enrichment, solid-phase alkylation-based anti-interference sample preparation, and narrow-bore nanoLC column for trace peptide separation and characterization. The method provided more than 8500 proteins from 1 L of bathypelagic seawater samples, which covered diverse microorganisms and crucial functions, e.g., the detection of key enzymes associated with the Wood-Ljungdahl pathway. Then, we applied SMMP to investigate vertical variations in the metabolic expression patterns of marine microorganisms from the euphotic zone to the bathypelagic zone. Methane oxidation and carbon monoxide (CO) oxidation were active processes, especially in the bathypelagic zone, which provided a remarkable energy supply for the growth and proliferation of heterotrophic microorganisms. In addition, marker protein profiles detected related to ammonia transport, ammonia oxidation, and carbon fixation highlighted that Thaumarchaeota played a critical role in primary production based on the coupled carbon-nitrogen process, contributing to the storage of carbon and nitrogen in the bathypelagic regions. SMMP has low microbial input requirements and yields in-depth metaproteome analysis, making it a prospective approach for comprehensive marine metaproteomic investigations.
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Proteômica , Água do Mar , Água do Mar/microbiologia , Água do Mar/química , Proteômica/métodos , Microbiota , Proteoma/análise , Proteoma/metabolismo , Metano/metabolismo , Metano/análise , Bactérias/metabolismo , Bactérias/isolamento & purificação , Oxirredução , Monóxido de Carbono/análise , Monóxido de Carbono/metabolismoRESUMO
BACKGROUND: Drought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses. RESULTS: TaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance. CONCLUSIONS: TaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.
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Secas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Fatores de Transcrição , Triticum , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Triticum/genética , Triticum/fisiologia , Triticum/metabolismo , Estresse Fisiológico/genética , Adaptação Fisiológica/genética , Genes de Plantas , Resistência à SecaRESUMO
BACKGROUND: We aimed to develop and validate a model to predict 1-year mortality risk among patients hospitalized for acute heart failure (AHF), build a risk score and interpret its application in clinical decision making. METHODS: By using data from China Patient-Centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, which prospectively enrolled patients hospitalized for AHF in 52 hospitals across 20 provinces, we used multivariate Cox proportional hazard model to develop and validate a model to predict 1-year mortality. RESULTS: There were 4,875 patients included in the study, 857 (17.58%) of them died within 1-year following discharge of index hospitalization. A total of 13 predictors were selected to establish the prediction model, including age, medical history of chronic obstructive pulmonary disease and hypertension, systolic blood pressure, Kansas City Cardiomyopathy Questionnaire-12 score, angiotensin converting enzyme inhibitor or angiotensin receptor blocker at discharge, discharge symptom, N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T, serum creatine, albumin, blood urea nitrogen, and highly sensitive C-reactive protein. The model showed a high performance on discrimination (C-index was 0.759 [95% confidence interval: 0.739, 0.778] in development cohort and 0.761 [95% confidence interval: 0.731, 0.791] in validation cohort), accuracy, calibration, and outperformed than several existed risk scores. A point-based risk score was built to stratify low- (0-12), intermediate- (13-16), and high-risk group (≥17) among patients. CONCLUSIONS: A prediction model using readily available predictors was developed and internal validated to predict 1-year mortality risk among patients hospitalized for AHF. It may serve as a useful tool for individual risk stratification and informing decision making to improve clinical care.
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Insuficiência Cardíaca , Hospitalização , Humanos , Insuficiência Cardíaca/mortalidade , Masculino , Feminino , China/epidemiologia , Idoso , Medição de Risco/métodos , Doença Aguda , Hospitalização/estatística & dados numéricos , Estudos Prospectivos , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Modelos de Riscos Proporcionais , Peptídeo Natriurético Encefálico/sangue , Troponina T/sangue , Proteína C-Reativa/análise , Fragmentos de Peptídeos/sangueRESUMO
To investigate the relationship between immune dynamic and graft-versus-host-disease (GVHD) risk, 111 initial diagnostic acute myeloid leukemia patients were reviewed. The flow cytometry data of 12 major lymphocyte subsets in bone marrow (BM) from 60 transplant patients at four different time points were analyzed. Additionally, 90 immune subsets in peripheral blood (PB) of 11 post-transplantation on day 100 were reviewed. Our results demonstrated that transplant patients had longer OS compared to non-transplant patients (Pâ <â 0.001). Among transplant patients, those who developed GVHD showed longer OS than those without GVHD (Pâ <â 0.05). URD donors and CMV-negative status donors were associated with improved OS in transplant patients (Pâ <â 0.05). Importantly, we observed a decreased Th/Tc ratio in BM at initial diagnostic in patients with GVHD compared to those without GVHD (Pâ =â 0.034). Receiver operating characteristic analysis indicated that a low Th/Tc ratio predicted an increased risk of GVHD with a sensitivity of 44.44% and specificity of 87.50%. Moreover, an increased T/NK ratio in BM of post-induction chemotherapy was found to be associated with GVHD, with a sensitivity of 75.76% and specificity of 65.22%. Additionally, we observed a decreased percentage of NK1 (CD56-CD16+NK) in PB on day 100 post-transplantation in the GVHD group (Pâ <â 0.05). These three indicators exhibit promising potential as specific and useful biomarkers for predicting GVHD. These findings provide valuable insights for the early identification and management of GVHD risk, thereby facilitating the possibility of improving patient outcomes.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Homólogo , Estudos RetrospectivosRESUMO
Nonspecific cross-linker can provide distance restraints between surface residues of any type, which could be used to investigate protein structure construction and protein-protein interaction (PPI). However, the vast number of potential combinations of cross-linked residues or sites obtained with such a cross-linker makes the data challenging to analyze, especially for the proteome-wide applications. Here, we developed SpotLink software for identifying site nonspecific cross-links at the proteome scale. Contributed by the dual pointer dynamic pruning algorithm and the quality control of cross-linking sites, SpotLink identified > 3000 cross-links from human cell samples within a short period of days. We demonstrated that SpotLink outperformed other approaches in terms of sensitivity and precision on the datasets of the simulated succinimidyl 4,4'-azipentanoate dataset and the condensin complexes with known structures. In addition, some valuable PPI were discovered in the datasets of the condensin complexes and the HeLa dataset, indicating the unique identification advantages of site nonspecific cross-linking. These findings reinforce the importance of SpotLink as a fundamental characteristic of site nonspecific cross-linking technologies.
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Proteoma , Software , Algoritmos , Reagentes de Ligações Cruzadas/química , HumanosRESUMO
MOTIVATION: Chemical cross-linking combined with mass spectrometry (CXMS) is now a well-established method for profiling existing protein-protein interactions (PPIs) with partially known structures. It is expected to map the results of CXMS with existing structure databases to study the protein dynamic profile in the structure analysis. However, currently available structure-based analysis software suffers from the difficulty of achieving large-scale analysis. Besides, it is infeasible for structure analysis and data mining on a large scale, since of lacking global measurement of dynamic structure mapping results. RESULTS: ComMap (protein complex structure mapping) is a software designed to perform large-scale structure-based mapping by integrating CXMS data with existing structures. It allows complete the distance calculation of PPIs with existing structures in batch within minutes and provides scores for different PPI-structure pairs of testable hypothetical structural dynamism via a global view. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Proteínas , Software , Reagentes de Ligações Cruzadas/química , Proteínas/química , Espectrometria de Massas/métodos , Mapeamento de Interação de Proteínas/métodosRESUMO
BACKGROUND: Alternaria alternata is the primary pathogen of potato leaf spot disease, resulting in significant potato yield losses globally. Endophytic microorganism-based biological control, especially using microorganisms from host plants, has emerged as a promising and eco-friendly approach for managing plant diseases. Therefore, this study aimed to isolate, identify and characterize the endophytic fungi from healthy potato leaves which had great antifungal activity to the potato leaf spot pathogen of A. alternata in vitro and in vivo. RESULTS: An endophytic fungal strain SD1-4 was isolated from healthy potato leaves and was identified as Talaromyces muroii through morphological and sequencing analysis. The strain SD1-4 exhibited potent antifungal activity against the potato leaf spot pathogen A. alternata Lill, with a hyphal inhibition rate of 69.19%. Microscopic and scanning electron microscope observations revealed that the strain SD1-4 grew parallel to, coiled around, shrunk and deformed the mycelia of A. alternata Lill. Additionally, the enzyme activities of chitinase and ß-1, 3-glucanase significantly increased in the hyphae of A. alternata Lill when co-cultured with the strain SD1-4, indicating severe impairment of the cell wall function of A. alternata Lill. Furthermore, the mycelial growth and conidial germination of A. alternata Lill were significantly suppressed by the aseptic filtrate of the strain SD1-4, with inhibition rates of 79.00% and 80.67%, respectively. Decrease of leaf spot disease index from 78.36 to 37.03 was also observed in potato plants treated with the strain SD1-4, along with the significantly increased plant growth characters including plant height, root length, fresh weight, dry weight, chlorophyll content and photosynthetic rate of potato seedlings. CONCLUSION: The endophyte fungus of T. muroii SD1-4 isolated from healthy potato leaves in the present study showed high biocontrol potential against potato leaf spot disease caused by A. alternata via direct parasitism or antifungal metabolites, and had positive roles in promoting potato plant growth.
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Alternaria , Endófitos , Doenças das Plantas , Folhas de Planta , Solanum tuberosum , Talaromyces , Alternaria/crescimento & desenvolvimento , Alternaria/fisiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Solanum tuberosum/microbiologia , Talaromyces/genética , Talaromyces/crescimento & desenvolvimento , Endófitos/fisiologia , Endófitos/isolamento & purificação , Endófitos/genética , Folhas de Planta/microbiologia , Hifas/crescimento & desenvolvimento , Antibiose , Quitinases/metabolismo , Agentes de Controle Biológico , Controle Biológico de Vetores/métodosRESUMO
BACKGROUND AND AIMS: Intestinal farnesoid X receptor (FXR) plays a critical role in alcohol-associated liver disease (ALD). We aimed to investigate whether alcohol-induced dysbiosis increased intestinal microRNA194 (miR194) that suppressed Fxr transcription and whether Lactobacillus rhamnosus GG-derived exosome-like nanoparticles (LDNPs) protected against ALD through regulation of intestinal miR194-FXR signaling in mice. APPROACH AND RESULTS: Binge-on-chronic alcohol exposure mouse model was utilized. In addition to the decreased ligand-mediated FXR activation, alcohol feeding repressed intestinal Fxr transcription and increased miR194 expression. This transcriptional suppression of Fxr by miR194 was confirmed in intestinal epithelial Caco-2 cells and mouse enteriods. The alcohol feeding-reduced intestinal FXR activation was further demonstrated by the reduced FXR reporter activity in fecal samples and by the decreased fibroblast growth factor 15 (Fgf15) messenger RNA (mRNA) in intestine and protein levels in the serum, which caused an increased hepatic bile acid synthesis and lipogeneses. We further demonstrated that alcohol feeding increased-miR194 expression was mediated by taurine-upregulated gene 1 (Tug1) through gut microbiota regulation of taurine metabolism. Importantly, 3-day oral administration of LDNPs increased bile salt hydrolase (BSH)-harboring bacteria that decreased conjugated bile acids and increased gut taurine concentration, which upregulated Tug1, leading to a suppression of intestinal miR194 expression and recovery of FXR activation. Activated FXR upregulated FGF15 signaling and subsequently reduced hepatic bile acid synthesis and lipogenesis and attenuated ALD. These protective effects of LDNPs were eliminated in intestinal FxrΔIEC and Fgf15-/- mice. We further showed that miR194 was upregulated, whereas BSH activity and taurine levels were decreased in fecal samples of patients with ALD. CONCLUSIONS: Our results demonstrated that gut microbiota-mediated miR194 regulation contributes to ALD pathogenesis and to the protective effects of LDNPs through modulating intestinal FXR signaling.
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Hepatopatias Alcoólicas , MicroRNAs , Animais , Humanos , Camundongos , Ácidos e Sais Biliares/metabolismo , Células CACO-2 , Etanol/farmacologia , Fígado/patologia , Hepatopatias Alcoólicas/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Taurina/farmacologia , NanopartículasRESUMO
Optical camera communication (OCC), which is enabled by large-scale light-emitting diodes (LEDs) arrays and image-sensor (IS) based cameras, has garnered significant attention from both researchers and industries. Existing OCC synchronization techniques typically rely on either super-Nyquist sampling or on computationally expensive asynchronous recovery algorithms to relax the required camera frame rate. In this paper, we propose a kurtosis-based asynchronous interference cancellation (K-AIC) algorithm, enabling the estimation for both the asynchronous interframe overlapping ratios and nonlinear Gamma distortion levels for each grayscale frame captured by camera. Through comprehensive numerical simulations, we demonstrate that the K-AIC algorithm exhibits low computational complexity, unique global optimum, high reliability and robust performance in mitigating asynchronous-induced bit errors across diverse scenarios. Short-range OCC experiment shows that the K-AIC scheme can effectively compensate for both interframe overlapping and Gamma distortions in a plesiochronous reception scenario, resulting in a Q-factor enhancement of approximately 12 dB with fluctuations of less than 1 dB. Consequently, the system achieves a net data rate of around 200 kbps.
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OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.
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Antimicrobial peptide (AMP) is an important component of crustaceans' innate immune system. In this study, a short neuropeptide F (sNPF) gene (Pc-sNPF) and a Forkhead box O (FOXO) gene (PcFOXO) from Procambarus clarkii were identified. Analysis findings showed that the expression level of AMP genes differed between male and female P. clarkii. Furthermore, Pc-sNPF and PcFOXO were related to the sex dimorphism of AMP. Knockdown of Pc-sNPF in the eyestalk significantly upregulated the expression of PcFOXO and two anti-lipopolysaccharide factors (PcALF4 and PcALFL) in the intestine of P. clarkii. The expression of PcFOXO in the intestine of female P. clarkii was higher than in that of males. Results from RNA interference revealed that PcFOXO positively regulated the expression of PcALF4 and PcALFL in the intestine of male and female P. clarkii. In summary, our study showed that differences in Pc-sNPF expression in eyestalk of male and female P. clarkii leading to sex dimorphism of AMP expression in the intestine are mediated by the sNPF-FOXO-AMP signal pathway called the eyestalk-intestine axis.
Assuntos
Proteínas de Artrópodes , Regulação da Expressão Gênica , Neuropeptídeos , Caracteres Sexuais , Animais , Masculino , Feminino , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/metabolismo , Regulação da Expressão Gênica/imunologia , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Astacoidea/genética , Astacoidea/imunologia , Intestinos , Peptídeos Antimicrobianos/genética , Peptídeos Antimicrobianos/metabolismo , Imunidade Inata/genética , Filogenia , Perfilação da Expressão Gênica , Sequência de Aminoácidos , Alinhamento de SequênciaRESUMO
OBJECTION: Inflammatory conditions and immune disorders may worsen the prognosis of chronic heart failure (CHF) patients. The aim of this study was to evaluate the prognostic value of a new indicator, C-NLR, composed of C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), for the risk of all-cause mortality in HF patients with different ejection fractions. METHODS: A total of 1221 CHF patients admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021 were enrolled in this study. All patients were divided into 2 groups according to the median C-NLR. Kaplan-Meier survival curves were used to compare the all-cause mortality among CHF patients with different ejection fractions. Cox proportional hazards analysis was used to evaluate the relationships between variables and mortality. The predictive value of the C-NLR was assessed by using receiver operating characteristic (ROC) analyses. RESULTS: We collected data from 1192 patients with CHF. Kaplan-Meier survival analysis revealed that patients with low LCR levels had better overall survival (OS). After multivariate adjustment Cox proportional hazards analysis, the level of C-NLR was still independently related to mortality. CONCLUSIONS: C-NLR was a competent independent predictor in HF with different ejection fractions, and routine measurement of C-NLR would help clinical doctors identify patients with a poor prognosis.
Assuntos
Insuficiência Cardíaca , Neutrófilos , Humanos , Neutrófilos/metabolismo , Prognóstico , Estudos Retrospectivos , Linfócitos/metabolismo , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismoRESUMO
OBJECTIVE: This study aimed to translate and culturally adapt the standardized outcomes in nephrology-hemodialysis fatigue (SONG-HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG-HD fatigue (C-SONG-HD fatigue) scale. METHODS: Forward and back translations were used to translate the SONG-HD fatigue scale into Chinese. We used the C-SONG-HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test-retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. RESULTS: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG-HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test-retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. CONCLUSION: The Chinese version of the SONG-HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients.